Dormant tumor cells constitute a population of cancer cells that reside in a non-proliferative or low-proliferative state, typically arrested in the G0/G1 phase and exhibiting minimal mitotic activity. These cells are commonly observed across multiple cancer types, including breast, lung, and ovarian cancers, and represent a central cellular component of minimal residual disease (MRD) following surgical resection of the primary tumor. Dormant cells are closely associated with long-term clinical latency and late-stage relapse. Due to their quiescent nature, dormant cells are intrinsically resistant to conventional therapies—such as chemotherapy and radiotherapy—that preferentially target rapidly dividing cells. In addition, they display enhanced anti-apoptotic capacity and immune evasion, rendering them particularly difficult to eradicate. More critically, in response to microenvironmental changes or activation of specific signaling pathways, dormant cells can re-enter the cell cycle and initiate metastatic outgrowth or tumor recurrence. This ability to escape dormancy underscores their clinical threat and positions their effective detection and elimination as a major challenge in contemporary cancer treatment. Hypoxia, a hallmark of the solid tumor microenvironment, has been widely recognized as a potent inducer of tumor cell dormancy. However, the molecular mechanisms by which tumor cells sense and respond to hypoxic stress—initiating the transition into dormancy—remain poorly defined. In particular, the lack of a systems-level understanding of the dynamic and multifactorial regulatory landscape has impeded the identification of actionable targets and constrained the development of effective therapeutic strategies. Accumulating evidence indicates that hypoxia-induced dormancy tumor cells are accompanied by a suite of adaptive phenotypes, including cell cycle arrest, global suppression of protein synthesis, metabolic reprogramming, autophagy activation, resistance to apoptosis, immune evasion, and therapy tolerance. These changes are orchestrated by multiple converging signaling pathways—such as PI3K-AKT-mTOR, Ras-Raf-MEK-ERK, and AMPK—that together constitute a highly dynamic and interconnected regulatory network. While individual pathways have been studied in depth, most investigations remain reductionist and fail to capture the temporal progression and network-level coordination underlying dormancy transitions. Systems biology offers a powerful framework to address this complexity. By integrating high-throughput multi-omics data—such as transcriptomics and proteomics—researchers can reconstruct global regulatory networks encompassing the key signaling axes involved in dormancy regulation. These networks facilitate the identification of core regulatory modules and elucidate functional interactions among key effectors. When combined with dynamic modeling approaches—such as ordinary differential equations—these frameworks enable the simulation of temporal behaviors of critical signaling nodes, including phosphorylated AMPK (p-AMPK), phosphorylated S6 (p-S6), and the p38/ERK activity ratio, providing insights into how their dynamic changes govern transitions between proliferation and dormancy. Beyond mapping trajectories from proliferation to dormancy and from shallow to deep dormancy, such dynamic regulatory models support topological analyses to identify central hubs and molecular switches. Key factors—such as NR2F1, mTORC1, ULK1, HIF-1α, and DYRK1A—have emerged as pivotal nodes within these networks and represent promising therapeutic targets. Constructing an integrative, systems-level regulatory framework—anchored in multi-pathway coordination, omics-layer integration, and dynamic modeling—is thus essential for decoding the architecture and progression of tumor dormancy. Such a framework not only advances mechanistic understanding but also lays the foundation for precision therapies targeting dormant tumor cells during the MRD phase, addressing a critical unmet need in cancer management.

A single-center, randomized, double-blind, dose-controlled trial of modified Sini Powder in treating mild to moderate generalized anxiety disorder(GAD) in the patients with syndrome of liver depression transforming into fire was conducted at Xiyuan Hospital, China Academy of Chinese Medical Sciences. A total of 80 patients with mild to moderate GAD and the syndrome of liver depression transforming into fire were included. Patients were assigned by the central randomization system at a ratio of 3∶1 into an observation group(n=60, receiving a conventional-dose of granules of modified Sini Powder) and a control group(n=20, receiving low-dose granules with the active ingredients being 50% of that in observation group). Assessments were conducted before treatment(baseline), after 2 weeks of introduction, after 2/4/8 weeks of treatment, and after 4 weeks of follow-up. The results were summarized as follows. In terms of primary outcome indicators, the observation group(62.2%) showed higher total response rate than the control group(26.6%)(P<0.05), and greater Hamilton anxiety scale(HAMA) score reduction after 8 weeks of treatment(P<0.05). In terms of secondary outcome indicators, the HAMA score(somatic anxiety score), traditional Chinese medicine(TCM) syndrome scores, Pittsburgh sleep quality index(PSQI) scale, and clinical global impression(CGI) scale score in the observation group showed a significant compared to the control group at each visit points(P<0.05). Adverse events occurred in 10 cases, including 9(16.9%) cases in the observation group and 1(6.6%) case in the control group. No adverse reaction was observed. In conclusion, conventional-dose modified Sini Powder demonstrated superior efficacy and favorable safety for mild and moderate GAD in the patients with the syndrome of liver depression transforming into fire over low-dose treatment.
Humans ; Male ; Female ; Adult ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/administration & dosage* ; Anxiety Disorders/drug therapy* ; Treatment Outcome ; Young Adult ; Powders ; Aged ; Liver/drug effects* ; Generalized Anxiety Disorder

BACKGROUND: Hypertension is associated with an increased risk of calcific aortic valve stenosis (CAVS). However, the directionality of causation between blood pressure traits and aortic stenosis is unclear, as is the benefit of antihypertensive drugs for CAVS. METHODS: Using genome-wide association studies (GWAS) summary statistics, we performed bidirectional two-sample univariable mendelian randomization (UVMR) to assess the causal associations of systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) with CAVS. Multivariable mendelian randomization (MVMR) was conducted to evaluate the direct effect of hypertension on CAVS, adjusting for confounders. Drug target mendelian randomization (MR) and summary-level MR (SMR) were used to estimate the effects of 12 classes of antihypertensive drugs and their target genes on CAVS risk. Inverse variance weighting was the primary MR method, with sensitivity analyses to validate results. RESULTS: UVMR showed SBP, DBP, and PP have causal effects on CAVS, with no significant reverse causality. MVMR confirmed the causality between hypertension and CAVS after adjusting for confounders. Drug-target MR analyses indicated that calcium channel blockers (CCBs), loop diuretics, and thiazide diuretics via SBP lowering exerted protective effects on CAVS risk. SMR analysis showed that the CCBs target gene CACNA2D2 and ARBs target gene AGTR1 were positively associated with CAVS risk, while diuretics target genes SLC12A5 and SLC12A1 were negatively associated with aortic stenosis risk. CONCLUSIONS Hypertension has a causal relationship with CAVS. Managing SBP in hypertensive patients with CCBs may prevent CAVS. ARBs might exert protective effects on CAVS independent of blood pressure reduction. The relationship between diuretics and CAVS is complex, with opposite effects through different mechanisms.

OBJECTIVE: To explore the efficacy and safety of Juan Bi Pill (JBP) in treatment of active rheumatoid arthritis (RA). METHODS: From February 2017 to May 2018, 115 participants from 4 centers were randomly divided into JBP group (57 cases) and placebo group (58 cases) in a 1:1 ratio using a random number table method. Participants received a dose of JBP (4 g, twice a day, orally) combined with methotrexate (MTX, 10 mg per week) or placebo (4 g, twice a day, orally) combined with MTX for 12 weeks. Participants were required with follow-up visits at 24 and 48 weeks, attending 7 assessment visits. Participants were undergo disease activity assessment 7 times (at baseline and 2, 4, 8, 12, 24, 48 weeks) and safety assessments 6 times (at baseline and 4, 8, 12, 24, 48 weeks). The primary endpoint was 28-joint Disease Activity Score (DAS28-ESR and DAS28-CRP). The secondary endpoints included American College of Rheumatology (ACR) criteria for 20% and 50% improvement (ACR20/50), Health Assessment Questionnaire Disability Index (HAQ-DI), clinical disease activity index (CDAI), visual analog scale (VAS), Short Form-36 (SF-36) score, Medial Outcomes Study (MOS) sleep scale score, serum erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tender joint count, swollen joint count, and morning stiffness. The adverse reactions were observed during the treatment. RESULTS: After 12 weeks of treatment, DAS28-ESR and DAS28-CRP scores in both groups were lower than before treatment (both P<0.01), while the remission rate of DAS28-ESR and DAS28-CRP and low disease activity of JBP group were higher than those in the placebo group (both P<0.01). JBP demonstrated better efficacy on ACR20 and ACR50 compliance rate at 12 and 48 weeks comparing to placebo (all P<0.05). The CDAI and HAQ-DI score, pain VAS and global VAS change of RA patients and physicians, the serum ESR and CRP levels, and the number of tenderness and swelling joints were lower than before treatment at 4, 8, 12, 24, 48 weeks in both groups (P<0.05 or P<0.01), while the reduction of above indices in the JBP group was more obvious than those in the placebo group at 12 weeks (ESR and CRP, both P<0.05) or at 12 and 48 weeks (all P<0.01). There was no difference in adverse reactions between the 2 groups during treatment (P=0.75). CONCLUSION JBP combined with MTX could effectively reduce disease activity in patients with RA in active stage, reduce the symptoms of arthritis, and improve the quality of life, while ensuring safety, reliability, and fewer adverse effects. (Trial Registration: ClinicalTrials.gov, No. NCT02885597).
Humans ; Arthritis, Rheumatoid/drug therapy* ; Methotrexate/adverse effects* ; Female ; Double-Blind Method ; Male ; Middle Aged ; Treatment Outcome ; Drugs, Chinese Herbal/adverse effects* ; Drug Therapy, Combination ; Adult ; Antirheumatic Agents/adverse effects* ; Aged

Objective To explore the effects of single-session table tennis exercise with different intensities on working memory and the associated cognitive neural processing mechanisms in college students with depressive symptoms by using event-related potential(ERP)technology.Methods A convenience sampling approach was employed to recruit 100 college students with depressive symptoms from a university.Participants were randomly assigned at a 1∶1∶1∶1 ratio to low-intensity exercise group,moderate-intensity exercise group,high-intensity exercise group,or control group.The exercise groups participated in a single 30-min table tennis intervention at intensities corresponding to 57%-64%of maximum heart rate(HRmax)and rate of perceived exertion(RPE)scores ranging from 9-11,65%-75%HRmax and RPE scores 12-13,and 76%-95%HRmax and RPE scores of 14-17(5-min warm-up,20-min monitored exercise,5-min cool-down).The control group did not receive any exercise intervention.Pre-and post-intervention assessments of verbal working memory(VWM)and spatial working memory(SWM)were performed,alongside the recording of ERP components,including the amplitude and latency of N2 and P3,during the tasks.Results A total of 91 participants(20 in the low-intensity exercise group,25 in the moderate-intensity exercise group,23 in the high-intensity exercise group,and 23 in the control group)were enrolled for analysis.In the VWM task,the main effect of time on accuracy was found to be significant(F(1,89)=5.942,P=0.017,partial η2=0.064).Post-intervention,accuracy was significantly improved in the moderate-intensity and high-intensity exercise groups(change=0.027,95%confidence interval[CI]0.001-0.053,P=0.037;change=0.029,95%CI 0.002-0.055,P=0.040).The main effect of time on reaction time was also significant(F(1,89)=7.244,P=0.009,partial η2=0.077).The interaction between group and time was also significant(F(3,87)=2.844,P=0.042,partial η2=0.089).After the intervention,the reaction time was reduced in the low-intensity and moderate-intensity exercise groups(change=-0.095,95%CI-0.183--0.007,P=0.035;change=-0.079,95%CI-0.158-0,P=0.049).The interaction between time and electrode location in the P3 latency in ERP components was significant(F(3,87)=5.785,P＜0.001,partial η2=0.062),while the interactions for other ERP measures were not significant(all P＞0.05).In the SWM task,the main effect of time on accuracy was significant(F(1,89)=5.092,P=0.027,partial η2=0.055),while the interaction between group and time was not significant(F(3,87)=0.799,P=0.498,partial η2=0.027).After the intervention,accuracy was improved in the moderate-intensity exercise group(change=0.019,95%CI 0-0.037,P=0.046).The main effect of time on reaction time was significant(F(1,89)=14.322,P＜0.001,partial η2=0.141).The interaction between group and time was not significant(F(3,87)=1.521,P=0.215,partial η2=0.050).After the intervention,reaction time was shortened in the moderate-intensity and high-intensity exercise groups(change=-0.082,95%CI-0.136--0.027,P=0.004;change=-0.075,95%CI-0.131--0.018,P=0.029).The interaction between time and electrode location in the P3 amplitude in ERP components was significant(F(3,87)=5.475,P=0.001,partial η2=0.059),while the interactions for other ERP measures were not significant(all P＞0.05).Conclusion Single-session table tennis exercise with different intensities has a positive effect on working memory in college students with depressive symptoms.Moderate-to high-intensity exercise can enhance VWM accuracy,while low-to moderate-intensity exercise can reduce VWM reaction time.Furthermore,moderate-intensity exercise can improve SWM accuracy,and moderate-to high-intensity exercise can shorten SWM reaction time.Additionally,high-intensity exercise can lead to greater activation of ERP components.

This study searched the clinical researches on traditional Chinese medicine （TCM） for cardiovascular diseases registered in Chinese Clinical Trial Registry and the US Clinical Trial Registry， the cardiovascular disease-related studies funded by the National Natural Science Foundation of China， as well as those published in China National Knowledge Infrastructure （CNKI）， Wanfang database， VIP.com， China Biology Medicine disc （CBMdisc）， Embase， Medline， Cochrane Library， and other databases published cardiovascular disease-related studies from 1 January 2021 to 30 June 2023. In order to analyse and evaluate the research progress of TCM treatment for coronary heart disease， hypertension， heart failure， and arrhythmia， this study aimed at recent research hotspots and research direction. It is found that the research on TCM for cardiovascular diseases was gradually deepening and the high-quality evidence continued to emerge. It is believed that studies related to the prevention and treatment of common cardiovascular diseases by TCM reflected the multi-angle integration of modern technology and pattern differentiation and treatment， closer integration of clinical and basic research， and further optimisation of pattern identification and interventions. On this basis， the research programme and implementation process should be further standardized， and the translation of research results should be emphasized to promote the standardized application and promotion of TCM diagnosis and treatment of cardiovascular diseases.

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

Objective:To analyze the eye lens dose and annual effective dose to interventional radiation workers in some hospitals of Xinxiang city from 2020 to 2022, and to ascertain the dose to interventional radiation workers.Methods:By using TLDs, the eye lens dose Hp(3) and annual effective dose Hp(10) were monitored for three consecutive years in six hospitals in Xinxiang city. The lens doses and annual effective doses to intervention radiation workers in different years in different-level hospitals and departments were analyzed. Results:From 2020 to 2022, a total of 117 people were monitored. The left eye lens dose range was 0.12-164.24 mSv, and the right eye lens dose range was 0.07-51.64 mSv. The average annual dose was 8.56 mSv for left eye lens and 4.49 mSv for right eye lens The average annual dose distribution in the MDL-5 mSv range for the left and right eye lens was 60.68% and 73.50%, respectively. 9.41% (11 people) of the left eye lens doses exceeded 20 mSv. The annual effective doses range was 0.11-31.27 mSv, with average annual dose of 2.56 mSv. The proportion of average annual effective doses mainly distributed in the range of MDL to 1.25 mSv was 52.14%, with 2.56% annual effective dose exceeding 20 mSv. There was no significant difference in left and right eye lens dose and annual effective dose between the tertiary hospitals and the secondary hospitals in three years ( P>0.05). Compared with different departments, the cumulative per capita dose in three years was statistically significant (left eye H=11.42, right eye H=13.72, annual effective dose H=25.94, P<0.05). The lens dose and annual effective dose in neurology department were lower than those in cardiology department and comprehensive intervention department ( Zcardiology department=-3.33, -3.78, -4.83, P<0.05; Zcomprehensive intervention department=-2.71, -2.63, -4.39, P<0.05). Conclusions:Most of the annual equivalent dose and annual effective dose to eye lens of the interventional radiation workers in Xinxiang city meet the national limits, but some of them have higher doses and exceed the national limits. It is suggested that the routine and continuous monitoring of eye lens doses to interventional radiologists should be strengthened while routine monitoring of annual effective dose, and attention should be paid to the eye lens and annual effective dose to interventional radiologists in secondary hospitals to improve the awareness of protection.